The revised application is in response to PA-06-543, "Mechanisms, Models, Measurement, &Management in Pain Research (R03)." Consistent with this program announcement, we aim to test hypotheses about the developmental pathways to comorbid pain and depressive disorders in females. Clinically significant pain disorders are markedly more common in individuals with depression, particularly in females who are more likely to experience both pain and depression from adolescence on. This is an issue of considerable public health significance, as depressed individuals who experience high levels of pain experience marked distress and functional impairment and are frequent consumers of medical services. Aims: The specific aims for this application are to address the following questions: 1) Are individual differences in behavioral and biological response to a pain stressor concurrently associated with depression and impairment at ages 10 and 12 and does this association grow stronger as puberty progresses;2) Do specific patterns of behavioral and biological response to a pain stressor explain variance in depression and functional impairment at ages 10 and 12;and 3) Are individual differences in response to a pain stressor at ages 10 and 12 prospectively associated with individual differences in depression and impairment at ages 11 and 13, after controlling for depression and impairment at ages 10 and 12? Approach: In the context of a longitudinal study currently funded by NIMH, Preadolescence precursors to depression in girls (R01 MH66167), 232 nine-year old girls are being assessed annually for a period of 5 years. Data are collected from both the girls and their mothers. We have embedded a pain stimulus into the longitudinal study, the cold pressor task (CPT), which was administered at age 10 and is planned for administration at age 12. We have collected saliva in response to the CPT age 10 and plan to collect samples again at age 12. There are no funds for assaying cortisol from the saliva or for conducting analyses on pain response in the parent R01. The purpose of this application for an R03 is to secure funding for testing hypotheses about the developmental phenomenology of comorbid pain and depression in females, an aim that was not included in the parent R01 study. Innovation: This will be the first study to explore the developmental interface between pain and depression using behavioral and biological responses to a controlled pain stimulus and clinically meaningful measures of depressive symptoms beginning in childhood. PUBLIC HEALTH RELEVANCE: Clinically significant pain disorders are much more common in individuals with depression, particularly in females who are more likely to experience both pain and depression from adolescence on. Given the impact of co-occurring pain and depression on public health for females especially, probing the developmental unfolding of the relations between depression and pain in girls is an important area of research. This will be the first study to explore the developmental interface between pain and depression using behavioral and biological responses to a controlled pain stimulus and clinically meaningful measures of depressive symptoms beginning in childhood.